Skip to main content
OpenTrials
Recruiting

NCT Number: NCT05253651

A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer

This study is being done to find out if tucatinib with other cancer drugs works better than standard of care to treat participants with HER2 positive colorectal cancer. This study will also determine what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.

Participants in this study have colorectal cancer that has spread through the body (metastatic) and/or cannot be removed with surgery (unresectable).

Participants will be assigned randomly to the tucatinib group or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either:

* mFOLFOX6 alone, * mFOLFOX6 with bevacizumab, or * mFOLFOX6 with cetuximab mFOLFOX6 is a combination of multiple drugs. All of the drugs given in this study are used to treat this type of cancer.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Colorectal Neoplasms Colonic Diseases Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centro de Investigacion Pergamino SA, Pergamino, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
  • Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment initiation to a central laboratory
  • If archival tissue is not available, a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to start of study treatment
  • HER2+ disease as determined by a tissue based assay performed at a central laboratory.
  • Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date.
  • Radiographically measurable disease per RECIST v1.1 with:
  • At least one site of disease that is measurable and that has not been previously irradiated, or
  • If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may have any of the following:
  • No evidence of brain metastases
  • Previously treated brain metastases which are asymptomatic

Exclusion criteria

  • Prior systemic anticancer therapy for colorectal cancer (CRC) in the locally advanced unresectable or metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization.
  • Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed >6 months prior to enrollment
  • Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
  • Previous treatment with anti-HER2 therapy
  • Ongoing Grade 3 or higher neuropathy
  • Active or untreated gastrointestinal (GI) perforation at the time of screening.

Treatment and study plan

Tucatinib

Drug

300mg given by mouth (orally) twice daily

Other names: TUKYSA, ONT-380, ARRY-380, PF-07265792

Trastuzumab

Drug

8mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 day 1, followed by 6mg/kg given by IV every 3 weeks thereafter.

Other names: Herceptin

Bevacizumab

Drug

5mg/kg given by IV every 2 weeks

Other names: Avastin

Cetuximab

Drug

400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly

Other names: Erbitux

Oxaliplatin

Drug

85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.

Leucovorin

Drug

400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.

Levoleucovorin

Drug

200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.

Fluorouracil

Drug

400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.

Primary outcomes

  1. Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR)

    Time frame: Up to approximately 3 years

    The time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause

Secondary outcomes

  1. Overall survival (OS)

    Time frame: Up to approximately 6 years

    The time from randomization to death from any cause

  2. Confirmed objective response rate (cORR) per RECIST v1.1 by BICR

    Time frame: Up to approximately 3 years

    The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by BICR

  3. PFS per RECIST v1.1 by investigator assessment

    Time frame: Up to approximately 3 years

    The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause

  4. cORR per RECIST v1.1 by investigator assessment

    Time frame: Up to approximately 3 years

    The proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by investigators

  5. Duration of response (DOR) per RECIST v1.1 by BICR

    Time frame: Up to approximately 3 years

    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause

  6. DOR per RECIST v1.1 by investigator assessment

    Time frame: Up to approximately 3 years

    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause

  7. Time to second progression or death (PFS2)

    Time frame: Up to approximately 3 years

    The time from randomization to disease progression on the next-line of therapy, or death from any cause

  8. Incidence of adverse events (AEs)

    Time frame: Through 30 days after the last study treatment; approximately 1 year

    Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

  9. Incidence of dose alterations

    Time frame: Through 30 days after the last study treatment; approximately 1 year

  10. Trough concentration (Ctrough)

    Time frame: Approximately 4 months

    PK parameter

  11. Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score

    Time frame: Through 30-37 days after the last study treatment; approximately 1 year

    Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/quality of life (QoL) scales, higher scores indicate better functioning or global health status/quality of life (QoL). For symptom scales, higher scores indicate greater symptom burden.

  12. Time to meaningful change in EORTC QLQ30 score

    Time frame: Through 30-37 days after the last study treatment; approximately 1 year

    The time from baseline to the first onset of a ≥10-point changes in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100.

    For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

Study contacts

Contact information is provided by the study sponsor or research team.

Pfizer CT.gov Call Center

CONTACT

[email protected]

1-800-718-1021

Sponsors and collaborators

Lead sponsor

Seagen, a wholly owned subsidiary of Pfizer

Industry

Registry information

Official study title

An Open-label Randomized Phase 3 Study of Tucatinib in Combination With Trastuzumab and mFOLFOX6 Versus mFOLFOX6 Given With or Without Either Cetuximab or Bevacizumab as First-line Treatment for Subjects With HER2+ Metastatic Colorectal Cancer

Acronym: MOUNTAINEER-03

Important dates

Study start
2022
Primary completion
2027
Study completion
2030
First posted
Feb 24, 2022
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.